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Archive - 2014

February 2nd

Same Protein Found Critical to Both Hematopoietic Stem Cell Function and Cancer Stem Cell Function

Researchers at the University of California, San Diego School of Medicine, and collaborating institutions have identified a protein critical to hematopoietic stem cell function and blood formation. The finding has potential as a new target for treating leukemia because cancer stem cells rely upon the same protein to regulate and sustain their growth. Hematopoietic stem cells give rise to all other blood cells. Writing in the February 2, 2014 advance online issue of Nature Genetics, principal investigator Tannishtha Reya, Ph.D., professor in the Department of Pharmacology, and colleagues found that a protein called Lis1 fundamentally regulates asymmetric division of hematopoietic stem cells, assuring that the stem cells correctly differentiate to provide an adequate, sustained supply of new blood cells. Asymmetric division occurs when a stem cell divides into two daughter cells of unequal inheritance: One daughter differentiates into a permanently specialized cell type while the other remains undifferentiated and capable of further divisions. "This process is very important for the proper generation of all the cells needed for the development and function of many normal tissues," said Dr. Reya. When cells divide, Lis1 controls orientation of the mitotic spindle, an apparatus of subcellular fibers that segregates chromosomes during cell division. "During division, the spindle is attached to a particular point on the cell membrane, which also determines the axis along which the cell will divide," Dr. Reya said. "Because proteins are not evenly distributed throughout the cell, the axis of division, in turn, determines the types and amounts of proteins that get distributed to each daughter cell. By analogy, imagine the difference between cutting the Earth along the equator versus halving it longitudinally.

A Cheaper, Faster, and Reliable Way to Detect Staph Infections in Under an Hour

Chances are you won't know you've have a staph infection until the test results come in, days after the symptoms first appear. But what if your physician could identify the infection much more quickly and without having to take a biopsy and ship it off for analysis? Researchers at the University of Iowa (UI) may have found a way to do this. The team has created a noninvasive chemical probe that detects a common species of staph bacteria in the body. The probe ingeniously takes advantage of staph's propensity to slash and tear at DNA, activating a beacon of sorts that lets doctors know where the bacteria are wreaking havoc. "We've come up with a new way to detect staph bacteria that takes less time than current diagnostic approaches," says Dr. James McNamara, assistant professor in internal medicine at the UI and the corresponding author of the paper published online on February 2, 2014 in Nature Medicine. "It builds on technology that's been around a long time, but with an important twist that allows our probe to be more specific and to last longer." The UI-developed probe targets Staphylococcus aureus, a species of staph bacteria common in hospitals and found in the general public as well. The bacteria causes skin infections, can spread to the joints and bones and can be fatal, particularly to those with weakened immune systems. "Every year in the U.S., half a million people become infected by S. aureusbacteria, and 20,000 of those who become infected die," adds Dr. Frank Hernandez, a post-doctoral researcher at the UI and first author on the paper.

Brain-Driven Prostheses Research Identifies Process by Which Brain Regions Can Cooperate When Necessary

Stanford researchers may have solved a riddle about the inner workings of the brain, which consists of billions of neurons, organized into many different regions, with each region primarily responsible for different tasks. The various regions of the brain often work independently, relying on the neurons inside that region to do their work. At other times, however, two regions must cooperate to accomplish the task at hand. The riddle is this: what mechanism allows two brain regions to communicate when they need to cooperate yet avoid interfering with one another when they must work alone? In a paper published online on February 2, 2014 in Nature Neuroscience, a team led by Stanford electrical engineering professor Dr. Krishna Shenoy reveals a previously unknown process that helps two brain regions cooperate when joint action is required to perform a task. "This is among the first mechanisms reported in the literature for letting brain areas process information continuously but only communicate what they need to," said Dr. Matthew T. Kaufman, who was a postdoctoral scholar in the Shenoy lab when he co-authored the paper. Dr. Kaufman initially designed his experiments to study how preparation helps the brain make fast and accurate movements – something that is central to the Shenoy lab's efforts to build prosthetic devices controlled by the brain. But the Stanford researchers used a new approach to examine their data that yielded some findings that were broader than arm movements. The Shenoy lab has been done pioneering work in analyzing how large numbers of neurons function as a unit. As they applied these new techniques to study arm movements, the researchers discovered a way that different regions of the brain keep results localized or broadcast signals to recruit other regions as needed.

Japanese Company Releases Data Indicating Fundamental Advance in Single-Molecule DNA and RNA Sequencing

On January 27, 2014, Quantum Biosystems, Inc., headquartered in Osaka, Japan, announced the release of raw data access to the first reads from its novel platform for electrical single-molecule DNA and RNA sequencing. The company released reads showing an accuracy of more than 99% in non-homopolymer regions and homopolymer indels at a rate of ~10%. This release allows researchers to evaluate the platform and engage in its validation and development. According to the company, this marks a major milestone in the single-molecule electrical sequencing of DNA. The work reported by Quantum Biosystems was completed using its breakthrough novel Quantum Sequencing platform (image). The platform allows the direct sequencing of single-stranded DNA and RNA without labeling or modification, on silicon devices that can be produced on the same production lines as consumer-grade integrated circuits. As the system uses no proteins or other reagents, it is potentially ultra-low cost, enabling consumer-level genome sequencing, according to the company. Based on research conducted at the University of Osaka, the Quantum Biosystems platform uses sub-nanometer gaps and picoamp-level currents to directly detect the conductance of single DNA and RNA molecules. This breakthrough in molecular sensing promises to bring about a fundamentally new class of sensors. Quantum Biosystems was formed in January of 2013 and is developing 4th-generation DNA and RNA sequencing systems for the low-cost and high-throughput analysis of whole genomes. While present systems require complicated sample preparation, and costly instruments, the Quantum Biosystems platform has no such barriers to entry and is well-positioned to bring about what some have called “the democratization of DNA sequencing,” Quantum Biosystems asserts.

January 31st

TCGA Study Identifies Potential Therapeutic Targets for Bladder Cancer

Investigators with The Cancer Genome Atlas (TCGA) Research Network have identified new potential therapeutic targets for a major form of bladder cancer, including important genes and pathways that are disrupted in the disease. They also discovered that, at the molecular level, some subtypes of bladder cancer – also known as urothelial carcinoma – resemble subtypes of breast, head and neck, and lung cancers, suggesting similar routes of development. The researchers' findings provide important insights into the mechanisms underlying bladder cancer, which is estimated will cause more than 15,000 deaths in the United States in 2014. TCGA is a collaboration jointly supported and managed by the National Cancer Institute (NCI) and the National Human Genome Research Institute (NHGRI), both parts of the National Institutes of Health. "TCGA Research Network scientists continue to unravel the genomic intricacies of many common and often intractable cancers, and these findings are defining new research directions and accelerating the development of new cancer therapies," said NIH Director Francis Collins, M.D., Ph.D. In this study, published online on January 29, 2014 in an open-access article in Nature, investigators examined bladder cancer that invades the muscle of the bladder, the deadliest form of the disease. The current standard treatments for muscle-invasive bladder cancer include surgery and radiation combined with chemotherapy. There are no recognized second-line therapies – second choices for treatments when the initial therapy does not work – and no approved targeted agents for this type of bladder cancer. Approximately 72,000 new cases of bladder cancer will be diagnosed in the United States in 2014.

January 31st

Tau-Induced Neurodegeneration Associated with Global Relaxation of Tightly-Wound DNA in Alzheimer’s Disease

In a study published online on January 26, 2014 in Nature Neuroscience, Bess Frost, Ph.D., from the Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, and co-authors, identify abnormal expression of genes, resulting from DNA relaxation, that can be detected in the brain and blood of Alzheimer's patients. The protein tau (image) is involved in a number of neurodegenerative disorders, including Alzheimer's disease. Previous studies have implicated DNA damage as a cause of neuron, or cell, death in Alzheimer's patients. Given that DNA damage can change the structure of DNA within cells, the researchers examined changes in DNA structure in tau-induced neurodegeneration. They used transgenic flies and mice expressing human tau to show that DNA is more relaxed in tauopathy. They then identified that the relaxation of tightly wound DNA and resulting abnormal gene expression are central events that cause neurons to die in Alzheimer's disease. The authors write, "Our work suggests that drugs that modify DNA structure may be beneficial for treating Alzheimer's Disease." The authors recommend, "A greater understanding of the pathway of DNA relaxation in tauopathies will allow us to identify the optimal target and explore the therapeutic potential of epigenetic-based drugs." The title of their article is, “Tau Promotes Neurodegeneration through Global Chromatin Relaxation.” [Press release] [Nature Neuroscience abstract]

Single Gene in Honeybees Influences Pollen-Basket Formation on Workers’ Hind Legs

A research team led by scientists from Wayne State University in Detroit, in collaboration with scientists from Michigan State University (MSU), has identified a single gene in honeybees that separates the queens from the workers. The scientists unraveled the gene's inner workings and published the results in the January 2014 issue of Biology Letters. The gene, which is responsible for leg and wing development, plays a crucial role in the evolution of bees' ability to carry pollen. "The gene — Ultrabithorax, or Ubx — is responsible for making hind legs different from fore legs so they can carry pollen" said Dr. Aleksandar Popadic, associate professor of biological sciences in Wayne State University's College of Liberal Arts and Science and principal investigator of the study. "In some groups, like crickets, Ubx is responsible for creating a 'jumping' hind leg. In others, such as bees, it makes a pollen basket — a 'naked,' bristle-free leg region that creates a space for packing pollen." "Other studies have shed some light on this gene's role in this realm, but our team examined in great detail how the modifications take place," added Dr. Zachary Huang, an MSU entomologist. Ubx represses the development of bristles on bees' hind legs, creating a smooth surface that can be used for packing pollen. This important discovery can be used as a foray into more commercial studies focused on providing means to enhance a bee's pollination ability – the bigger the pollen basket, the more pollen that can be packed in it and transported back to the hive. While workers have these distinct features, queens do not. The team confirmed this by isolating and silencing Ubx. This made the pollen baskets completely disappear, altered the growth of the pollen comb, and reduced the size of the pollen press.

Centrosome-Related Signaling Problem Can Cause Autosomal Recessive Primary Microcephaly

Professor Erich Nigg and his research group at the Biozentrum of the University of Basel in Switzerland have discovered an amino acid signal essential for error-free cell division. This signal regulates the number of centrosomes in the cell, and its absence results in the development of pathologically altered cells. Remarkably, such altered cells are found in people with a neurodevelopmental disorder called autosomal recessive primary microcephaly. The results of these investigations have been published online on January 30, 2014 in Current Biology. Cell division is the basis of all life. Of central importance is the error-free segregation of genetic material, the chromosomes. A flawless division process is a prerequisite for the development of healthy, new cells, whilst errors in cell division can cause illnesses such as cancer. The centrosome, a tiny cell organelle, plays a decisive role in this process. Professor Nigg’s research group at the Biozentrum of the University of Basel has investigated an important step in cell division: the duplication of the centrosome and its role in the correct segregation of the chromosomes into two daughter cells. The protein STIL has an essential function in this process. It ensures that centrosome duplicate before one half of the genetic material is transported into each of the two daughter cells. During cell division, the protein STIL is degraded. If this does not occur, the protein accumulates in the cell, which then causes an overproduction of centrosomes. As a consequence, mis-segregated chromosomes are incorporated into the daughter cells, which then represent cells with faulty genetic material.

Gastric Bypass and Mysterious Recovery from Type 2 Diabetes

The majority of gastric bypass patients mysteriously recover from their type 2 diabetes within days, before any weight loss has taken place. A study at Lund University Diabetes Centre in Sweden has now shown that the insulin-producing beta cells increase in number and performance after the surgery. "We have suspected this for a while, but there have not previously been any models to prove it," says Dr Nils Wierup, who led the research. The small study involved gastric bypass surgery on just four pigs, but is the only study of its kind and therefore unique. The results confirm that neither weight loss nor reduced food intake are required in order for the procedure to raise the number of beta cells, as the pigs had identical body weight and ate exactly the same amount of food. Type 2 diabetes develops when the body's insulin-producing beta cells stop working, or when the body is not able to use the insulin that the cells produce. The majority of people who suffer from obesity and undergo a gastric bypass operation recover from their diabetes within days of the procedure. The operation involves altering the connection between the stomach and the intestines so that food bypasses the stomach and parts of the small intestine and instead goes straight into the small intestine. Until now, it has been a mystery why patients' blood sugar levels normalize. The group at Lund University Diabetes Centre found that the pigs' beta cells improve their insulin secretion. The researchers also studied tissue from the pigs' pancreas, the organ where the beta cells are located, something that is almost impossible to do in humans. They found that the number of beta cells increased after the operation. The group have previously studied the effects of gastric bypass on humans.

Wolves Are Better Imitators of Conspecifics Than Dogs, Learning More Effectively

Although wolves and dogs are closely related, they show some striking differences. Scientists from the Messerli Research Institute at the University of Veterinary Medicine, Vienna have undertaken experiments that suggest that wolves observe one another more closely than dogs and so are better at learning from one another. The scientists believe that cooperation among wolves is the basis of the understanding between dogs and humans. Their findings have been published online on January 29, 2014 in an open-access article in PLOS ONE. Wolves were domesticated more than 15,000 years ago and it is widely assumed that the ability of domestic dogs to form close relationships with humans stems from changes during the domestication process. But the effects of domestication on the interactions between the animals have not received much attention. The point has been addressed by Dr. Friederike Range and Dr. Zsófia Virányi, two members of the University of Veterinary Medicine, Vienna (Vetmeduni Vienna) who work at the Wolf Science Center (WSC) in Ernstbrunn, Niederösterreich. The scientists found that wolves are considerably better than dogs at opening a container, providing they have previously watched another animal do so. Their study involved 14 wolves and 15 mongrel dogs, all about six months old, hand-reared and kept in packs. Each animal was allowed to observe one of two situations in which a trained dog opened a wooden box, either with its mouth or with its paw, to gain access to a food reward. Surprisingly, all of the wolves managed to open the box after watching a dog solve the puzzle, while only four of the dogs managed to do so. Wolves more frequently opened the box using the method they had observed, whereas the dogs appeared to choose randomly whether to use their mouth or their paw.